In this revised K99 application, Sandra L. Deming, Ph.D, MPH proposes a comprehensive five-year career development plan encompassing both didactic and research training at Vanderbilt University Medical Center, an environment richly capable of providing the education, training, and mentorship necessary to achieve her goal of becoming an independent cancer and molecular epidemiologist. The multi-faceted training plan including education and research training in cancer biology, statistical genetics, molecular epidemiology, and bioinformatics, was designed in conjunction with her highly experienced mentors, Dr. Wei Zheng and Dr. Jonathan Haines, to fill gaps in her education and training. Following the training period, Dr. Deming will directly apply her newly acquired knowledge and skills to a focused research plan that will expand our understanding of the relationships between genetic susceptibility related to circadian rhythms, melatonin pathways, and breast cancer risk. Research project rationale: Currently, the etiology of most breast cancers is still unaccounted for, which is of concern given that breast cancer is the most frequently occurring cancer among women worldwide. Recent data from observational and laboratory studies have lead to the hypotheses that light at night and sleep exposures, along with genetic susceptibility due to genes in the melatonin and circadian pathways may be associated with altered breast cancer risk. Design: The candidate will genotype 114 polymorphisms in the genes of the circadian and melatonin pathways and assess their interaction with light at night and sleep exposures in breast cancer risk among individuals in the Shanghai Breast Cancer Study. The cumulative effect of this carefully developed training and research program will: 1) provide valuable understanding of these pathways and their association with breast cancer risk;2) result in the submission of highly competitive R01 applications in the later years of this award period;and 3) launch this candidate's career as an independent researcher in cancer and molecular epidemiology. RELEVANCE: Breast cancer is the most common cancer among women worldwide, however the cause of most cases is still unknown. Understanding the role of circadian and melatonin genes, and the interaction those genes with light at night and sleep exposures in breast cancer risk may aid in the identification of individuals at higher risk for the disease and allow for targeting of these individuals with preventive strategies.